Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Multiple Annular Plaques on Both Legs Ignacio Gómez-Martín, MD; Gemma Martín-Ezquerra, MD, PhD; Daniel López Aventín, MD
Amaninhis40spresentedwitha3-weekhistoryofmultipleerythematous annular plaques on both legs. The patient reported that these lesions had appeared as erythematous and pruritic papules that had grown in number and size, presenting a centrifugal spread. No associatedsystemicsymptomswerepresent.Treatmentwithtopicalantifungalsandcorticosteroidshadfailedtoimprovethelesions.Sixweeksbefore, the patient had undergone a renal colic that was treated with nonsteroidalanti-inflammatorydrugsandopioidderivatives.Noinsectbites or other triggering factors were recorded. His medical history included penicillin allergy, dyslipidemia, kidney stones, and allergic rhinitis. Physical examination disclosed multiple erythematous to violaceous, annular, nonscaly plaques, from 4 to 30 cm in diameter, with
A
raised erythematous borders on the inner aspect of both legs (Figure, A). No enlarged regional lymph nodes were noted, and the rest of the physical examination had unremarkable results. A complete blood cell count and biochemical profile only revealed a peripheral eosinophilia (1100 cells/μL [to convert to ×109 cells per liter, multiply by 0.001]). Serologic testing for Borrelia burgdorferi, Rickettsia conorii, and Rickettsia typhi yielded negative results. Neither antinuclear antibodies nor increased tumoral marker levels were detected. Two skin biopsy specimens were obtained showing identical histopathological features (Figure, B and C). What is your diagnosis?
B
C
Figure. A, Several plaques with raised erythematous borders on both lower legs. B, Skin biopsy specimen showing perivascular and interstitial inflammatory infiltrate composed of conspicuous eosinophils in addition to lymphocytes, histiocytes, and purpura in superficial dermis (hematoxylin-eosin, original magnification ×100). C, Perivascular and interstitial inflammatory infiltrate composed of numerous eosinophils with focal degranulation, in addition to lymphocytes and histiocytes in the upper dermis, was noted in both skin biopsy specimens (hematoxylin-eosin, original magnification ×200).
jamadermatology.com
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
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895
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Eosinophilic annular erythema
Microscopic Findings and Clinical Course Histopathologic examination demonstrated a moderate to dense superficial, perivascular, and interstitial inflammatory infiltrate mainly composed of eosinophils in addition to lymphocytes and few histiocytes (Figure, B and C). Degranulation of eosinophils was identified, but no flame figures were present. Neither leukocytoclasis nor vessel wall necrosis was found. Direct immunofluorescence study from perilesional skin samples failed to detect specific deposits. Treatment with oral prednisone (30 mg/d) was prescribed, and a dramatic response of skin lesions and pruritus was observed within 2 weeks. The dose of prednisone was tapered, and the treatment was withdrawn after 2 months. At that time, only discrete residual hyperpigmented macules were present. No relapse has occurred after the 1-year follow-up period.
Discussion Eosinophilic annular erythema (EAE) is a rare benign annular dermatitis that combines a figurate pattern and tissue eosinophilia. It was initially reported in children as annular erythema of infancy by Peterson and Jarratt in 1981.1 The disease manifests clinically as multiple erythematous papules with centrifugal spreading and central clearing to form annular or polycyclic persistent plaques with a raised border. The annular plaques are of variable size and are often distributed symmetrically, mainly involving the trunk and extremities, although the face can also be affected.2 The lesions are asymptomatic or mildly pruriginous. Eosinophilic annular erythema follows a chronic course (from weeks to months) with frequent relapses. The eruption, however, tends to heal spontaneously or after treatment without sequelae, giving rise to residual and transient hyperpig-
mented macules. The diagnosis of EAE is established on the basis of characteristic clinicopathological features and negative results of direct immunofluorescence tests. Clinically, the differential diagnosis should include the wide group of figurate erythemas (erythema annulare centrifugum, subacute cutaneous lupus erythematosus, erythema chronicum migrans, erythema gyratum repens, granuloma annulare, annular erythemas of infancy), urticaria, prebullous bullous pemphigoid, insect bites, and cutaneous adverse drug reactions.3 The histologic analysis is not specific but shows a superficial and deep perivascular dermal inflammatory infiltrate consisting of lymphocytes, histiocytes, and numerous eosinophils. Basal vacuolar degeneration and mucin deposition are sometimes observed. Histologically, the main differential diagnosis is Wells syndrome (eosinophilic cellulitis). There is controversy over whether to consider EAE a distinct entity or an atypical annular variant of Wells syndrome.4 Eosinophilic degranulation, flame figures, and granulomatous reaction (frequently found in Wells syndrome) are usually absent in EAE but may occasionally be present depending on the stage of evolution when skin biopsy is performed.5 In EAE, constitutional symptoms such as fever or malaise have rarely been reported. Exceptionally, EAE has been associated with autoimmune thyroid disease, chronic borreliosis, renal carcinoma, chronic gastritis, diabetes mellitus, chronic hepatitis C virus infection, and chronic kidney disease.5,6 Treatment with systemic corticosteroids usually achieves a rapid improvement of the lesions, although relapses after dose reduction or withdrawal of the therapy are not uncommon.4 Antimalarial therapy alone or in combination with steroids has also been reported to be an effective therapeutic option.7 In resistant cases, indomethacin, minocycline, low-dose cyclosporine, or oral antihistamines combined with dapsone have shown variable therapeutic responses. Spontaneous resolution has also been reported.8
Author Affiliations: Department of Dermatology, Hospital del Mar, Barcelona, Spain.
2. Toledo-Alberola F, Betlloch-Mas I. Annular erythema of infancy [in Spanish]. Actas Dermosifiliogr. 2010;101(6):473-484.
Corresponding Author: Ignacio Gómez-Martín, MD, Department of Dermatology, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain ([email protected]).
3. Ríos-Martín JJ, Ferrándiz-Pulido L, Moreno-Ramírez D. Approaches to the dermatopathologic diagnosis of figurate lesions [in Spanish]. Actas Dermosifiliogr. 2011;102(5):316-324.
Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD.
4. Howes R, Girgis L, Kossard S. Eosinophilic annular erythema: a subset of Wells’ syndrome or a distinct entity? Australas J Dermatol. 2008;49(3): 159-163.
Published Online: June 18, 2014. doi:10.1001/jamadermatol.2014.45.
5. El-Khalawany M, Al-Mutairi N, Sultan M, Shaaban D. Eosinophilic annular erythema is a peculiar subtype in the spectrum of Wells syndrome: a multicentre long-term follow-up study. J Eur Acad Dermatol Venereol. 2013;27(8):973-979.
ARTICLE INFORMATION
Conflict of Interest Disclosures: None reported. REFERENCES
6. Rongioletti F, Fausti V, Kempf W, Rebora A, Parodi A. Eosinophilic annular erythema: an expression of the clinical and pathological polymorphism of Wells syndrome. J Am Acad Dermatol. 2011;65(4):e135-e137. 7. Mebazaa A, Kenani N, Ghariani N, et al. Eosinophilic annular erythema responsive to chloroquin. Eur J Dermatol. 2009;19(1):84-85. 8. Prajapati V, Cheung-Lee M, Schloss E, Salopek TG. Spontaneously resolving eosinophilic annular erythema. J Am Acad Dermatol. 2012;67(2):e75-e77.
1. Peterson AO Jr, Jarratt M. Annular erythema of infancy. Arch Dermatol. 1981;117(3):145-148.
896
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Multiple Annular Plaques on Both Legs Ignacio Gómez-Martín, MD; Gemma Martín-Ezquerra, MD, PhD; Daniel López Aventín, MD
Amaninhis40spresentedwitha3-weekhistoryofmultipleerythematous annular plaques on both legs. The patient reported that these lesions had appeared as erythematous and pruritic papules that had grown in number and size, presenting a centrifugal spread. No associatedsystemicsymptomswerepresent.Treatmentwithtopicalantifungalsandcorticosteroidshadfailedtoimprovethelesions.Sixweeksbefore, the patient had undergone a renal colic that was treated with nonsteroidalanti-inflammatorydrugsandopioidderivatives.Noinsectbites or other triggering factors were recorded. His medical history included penicillin allergy, dyslipidemia, kidney stones, and allergic rhinitis. Physical examination disclosed multiple erythematous to violaceous, annular, nonscaly plaques, from 4 to 30 cm in diameter, with
A
raised erythematous borders on the inner aspect of both legs (Figure, A). No enlarged regional lymph nodes were noted, and the rest of the physical examination had unremarkable results. A complete blood cell count and biochemical profile only revealed a peripheral eosinophilia (1100 cells/μL [to convert to ×109 cells per liter, multiply by 0.001]). Serologic testing for Borrelia burgdorferi, Rickettsia conorii, and Rickettsia typhi yielded negative results. Neither antinuclear antibodies nor increased tumoral marker levels were detected. Two skin biopsy specimens were obtained showing identical histopathological features (Figure, B and C). What is your diagnosis?
B
C
Figure. A, Several plaques with raised erythematous borders on both lower legs. B, Skin biopsy specimen showing perivascular and interstitial inflammatory infiltrate composed of conspicuous eosinophils in addition to lymphocytes, histiocytes, and purpura in superficial dermis (hematoxylin-eosin, original magnification ×100). C, Perivascular and interstitial inflammatory infiltrate composed of numerous eosinophils with focal degranulation, in addition to lymphocytes and histiocytes in the upper dermis, was noted in both skin biopsy specimens (hematoxylin-eosin, original magnification ×200).
jamadermatology.com
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
895
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Eosinophilic annular erythema
Microscopic Findings and Clinical Course Histopathologic examination demonstrated a moderate to dense superficial, perivascular, and interstitial inflammatory infiltrate mainly composed of eosinophils in addition to lymphocytes and few histiocytes (Figure, B and C). Degranulation of eosinophils was identified, but no flame figures were present. Neither leukocytoclasis nor vessel wall necrosis was found. Direct immunofluorescence study from perilesional skin samples failed to detect specific deposits. Treatment with oral prednisone (30 mg/d) was prescribed, and a dramatic response of skin lesions and pruritus was observed within 2 weeks. The dose of prednisone was tapered, and the treatment was withdrawn after 2 months. At that time, only discrete residual hyperpigmented macules were present. No relapse has occurred after the 1-year follow-up period.
Discussion Eosinophilic annular erythema (EAE) is a rare benign annular dermatitis that combines a figurate pattern and tissue eosinophilia. It was initially reported in children as annular erythema of infancy by Peterson and Jarratt in 1981.1 The disease manifests clinically as multiple erythematous papules with centrifugal spreading and central clearing to form annular or polycyclic persistent plaques with a raised border. The annular plaques are of variable size and are often distributed symmetrically, mainly involving the trunk and extremities, although the face can also be affected.2 The lesions are asymptomatic or mildly pruriginous. Eosinophilic annular erythema follows a chronic course (from weeks to months) with frequent relapses. The eruption, however, tends to heal spontaneously or after treatment without sequelae, giving rise to residual and transient hyperpig-
mented macules. The diagnosis of EAE is established on the basis of characteristic clinicopathological features and negative results of direct immunofluorescence tests. Clinically, the differential diagnosis should include the wide group of figurate erythemas (erythema annulare centrifugum, subacute cutaneous lupus erythematosus, erythema chronicum migrans, erythema gyratum repens, granuloma annulare, annular erythemas of infancy), urticaria, prebullous bullous pemphigoid, insect bites, and cutaneous adverse drug reactions.3 The histologic analysis is not specific but shows a superficial and deep perivascular dermal inflammatory infiltrate consisting of lymphocytes, histiocytes, and numerous eosinophils. Basal vacuolar degeneration and mucin deposition are sometimes observed. Histologically, the main differential diagnosis is Wells syndrome (eosinophilic cellulitis). There is controversy over whether to consider EAE a distinct entity or an atypical annular variant of Wells syndrome.4 Eosinophilic degranulation, flame figures, and granulomatous reaction (frequently found in Wells syndrome) are usually absent in EAE but may occasionally be present depending on the stage of evolution when skin biopsy is performed.5 In EAE, constitutional symptoms such as fever or malaise have rarely been reported. Exceptionally, EAE has been associated with autoimmune thyroid disease, chronic borreliosis, renal carcinoma, chronic gastritis, diabetes mellitus, chronic hepatitis C virus infection, and chronic kidney disease.5,6 Treatment with systemic corticosteroids usually achieves a rapid improvement of the lesions, although relapses after dose reduction or withdrawal of the therapy are not uncommon.4 Antimalarial therapy alone or in combination with steroids has also been reported to be an effective therapeutic option.7 In resistant cases, indomethacin, minocycline, low-dose cyclosporine, or oral antihistamines combined with dapsone have shown variable therapeutic responses. Spontaneous resolution has also been reported.8
Author Affiliations: Department of Dermatology, Hospital del Mar, Barcelona, Spain.
2. Toledo-Alberola F, Betlloch-Mas I. Annular erythema of infancy [in Spanish]. Actas Dermosifiliogr. 2010;101(6):473-484.
Corresponding Author: Ignacio Gómez-Martín, MD, Department of Dermatology, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain ([email protected]).
3. Ríos-Martín JJ, Ferrándiz-Pulido L, Moreno-Ramírez D. Approaches to the dermatopathologic diagnosis of figurate lesions [in Spanish]. Actas Dermosifiliogr. 2011;102(5):316-324.
Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD.
4. Howes R, Girgis L, Kossard S. Eosinophilic annular erythema: a subset of Wells’ syndrome or a distinct entity? Australas J Dermatol. 2008;49(3): 159-163.
Published Online: June 18, 2014. doi:10.1001/jamadermatol.2014.45.
5. El-Khalawany M, Al-Mutairi N, Sultan M, Shaaban D. Eosinophilic annular erythema is a peculiar subtype in the spectrum of Wells syndrome: a multicentre long-term follow-up study. J Eur Acad Dermatol Venereol. 2013;27(8):973-979.
ARTICLE INFORMATION
Conflict of Interest Disclosures: None reported. REFERENCES
6. Rongioletti F, Fausti V, Kempf W, Rebora A, Parodi A. Eosinophilic annular erythema: an expression of the clinical and pathological polymorphism of Wells syndrome. J Am Acad Dermatol. 2011;65(4):e135-e137. 7. Mebazaa A, Kenani N, Ghariani N, et al. Eosinophilic annular erythema responsive to chloroquin. Eur J Dermatol. 2009;19(1):84-85. 8. Prajapati V, Cheung-Lee M, Schloss E, Salopek TG. Spontaneously resolving eosinophilic annular erythema. J Am Acad Dermatol. 2012;67(2):e75-e77.
1. Peterson AO Jr, Jarratt M. Annular erythema of infancy. Arch Dermatol. 1981;117(3):145-148.
896
JAMA Dermatology August 2014 Volume 150, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Georgetown University Medical Center User on 05/22/2015
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![[Hyperpigmented, asymptomatic, annular plaques with satellite lesions].](/assets/img/hold.png)
